alexa Reduced exposure of imatinib after coadministration with acetaminophen in mice
Agri and Aquaculture

Agri and Aquaculture

Fisheries and Aquaculture Journal

Author(s): Inthisham Nassar

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Purpose:
Imatinib is an efficacious drug against chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) due to selective inhibition of c-KIT and BCR-ABL kinases. It presents almost complete bioavailability, is eliminated via P450-mediated metabolism and is well tolerated. However, a few severe drug-drug interactions have been reported in cancer patients taking acetaminophen.
Materials and Methods:
Male ICR mice were given 100 mg/kg single dose of imatinib orally or imatinib 100 mg/kg (orally) coadministered with acetaminophen intraperitoneally (700 mg/kg). Mice were euthanized at predetermined time points, blood samples collected, and imatinib plasma concentration measured by HPLC.
Results:
Imatinib AUC0-12 was 27.04 ± 0.38 mg·h/ml, Cmax was 7.21 ± 0.99 mg/ml and elimination half-life was 2.3 hours. Acetaminophen affected the imatinib disposition profile: AUC0-12 and Cmax decreased 56% and 59%, respectively and a longer half-life was observed (5.6 hours).
Conclusions:
The study shows a pharmacokinetic interaction between acetaminophen and imatinib which may render further human studies necessary if both drugs are administered concurrently to cancer patients.

This article was published in Indian Journal of Pharmacology and referenced in Fisheries and Aquaculture Journal

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